Hearing impairment is a common sensory deficit with both genetic and environmental etiologies. Given the complexity of the auditory system, it is not surprising that a broad range of gene products have been implemented in hearing loss. This wealth of genetic heterogeneity provides numerous targets for mutations that may alter auditory abilities and provides an avenue which novel can discover genes or the function of previously cloned genes can be characterized further. However, this heterogeneity also complicates clinical diagnosis. Molecular genetic studies to dissect this complexity will allow clinicians to diagnose precisely the molecular lesion underlying a hearing loss disorder, which should facilitate the most appropriate intervention. Characterization of modifier genes that may rescue or increase the auditory consequences of a particular mutation in a hearing impaired family may provide predictive value in counseling patients carrying these mutations and genetic variations. Deficits in auditory function at any age can lead to isolation and withdrawal from the hearing population. Therefore it is imperative for hearing researchers to better understand the auditory system and search for mechanisms to curb or cure hearing impairment. A molecular genetic and animal model approach as described in this grant proposal is one path to follow towards accomplishing this task.